For the past 19 years, we have conducted large randomized controlled trials with out-of- treatment people who inject drugs (PWID) in Denver. This research has been focused on facilitating substance use treatment entry and retention as a means of reducing HIV risk behaviors and drug use. While this work has added substantially to our knowledge of risk behaviors and risk reduction strategies in the short term, major questions remain unanswered regarding the life course of these behaviors. In this proposal, we will assess long term changes in HIV risk behaviors and drug use among PWID with a goal of describing and evaluating the natural history of PWID and identifying important predictors of life course behaviors of PWID. It is hypothesized that HIV risk behaviors, opiate use and mortality will be affected by major life events, such as overdose, incarceration, and policy changes. Also, patterns of HIV risk behavior and drug use maybe affected by other factors such as gender, ethnicity and age. This study will contribute to the literature on prevention of HIV risk behavior and reduction in morbidity and mortality over the life course in this highly vulnerable population of PWID.